Decreased expression of MBD2 and MBD4 gene and genomic-wide hypomethylation in patients with primary immune thrombocytopenia.

ABSTRACT

Genome-wide hypomethylation has been confirmed in patients with primary immune thrombocytopenia (ITP). Proteins containing methylcytosine-binding domain (MBD) are involved in promoter methylation as transcriptional repressors and promote the gene-silencing effect of DNA methylation. The purpose of this study was to investigate the methylation pattern of T cells and the relationship between genomic methylation and the expression of MBD2 and MBD4 in ITP patients. DNA deoxymethylcytosine content of CD4(+) cells from peripheral blood mononuclear cells was measured by enzyme-linked immunoassay. Real-time polymerase chain reaction was performed to quantify the transcription levels of MBD2 and MBD4 in peripheral blood mononuclear cells and CD4(+) cells. DNA dmC content in CD4(+) cells of ITP patients was significantly lower than in the controls (p = 0.001). The mRNA level of MBD2 and MBD4 in CD4(+) cells of ITP patients was statistically lower than those of the controls (p < 0.001). Positive correlations between methylation indexes and expression of each enzyme were observed in the control group (r(2) = 0.718, p = 0.004 for MBD2; r(2) = 0.608, p = 0.015 for MBD4). However, inverse correlations were found in ITP patients (r(2) = 0.604, p = 0.008 for MBD2; r(2) = 0.498, p = 0.027 for MBD4). Our results indicate that decreased expression of MBD2 and MBD4 might involve in the pathogenesis of ITP.